title: Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency.
abstract: OBJECTIVE
  We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD).
  
  
  METHODS
  Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were GH-naïve at baseline and GH-treated in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study.
  
  
  METHODS
  Development of MPHD was assessed from investigator diagnoses, adverse events, and concomitant medications. Analyses were performed for all patients and for those who developed MPHD within 4.5 years or had ≥3.5 years, follow-up and continued to have IGHD (4-year cohort).
  
  
  RESULTS
  MPHD developed in 118/5805 (2.0%) children overall, and in 96/1757 (5.5%) in the 4-year cohort. Patients who developed MPHD had more profound GHD, with decreased height SDS, IGF1 SDS and peak stimulated GH, and greater height decrement vs target, compared with children who continued to have IGHD (P<0.001 for each variable). Delivery complications, congenital anomalies, and perinatal/neonatal adverse events occurred more frequently in patients who developed MPHD. The most frequent additional deficiency was TSH (82 patients overall); four patients developed two pituitary hormone deficiencies and one developed three deficiencies. Multivariable logistic regression indicated that years of follow-up (odds ratio 1.55), baseline age (1.17), baseline height SDS (0.69), and peak stimulated GH (0.64) were associated with the development of MPHD.
  
  
  CONCLUSIONS
  MPHD is more likely to develop in patients with more severe idiopathic IGHD. Older baseline age, lower baseline height SDS, and longer follow-up duration are associated with increased risk of development of MPHD.
authors.affiliation: Lilly Deutschland GmbH, Werner-Reimers-Strasse 2-4, 61352 Bad Homburg, Germany.
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Cheri
authors.initials: C
authors.lastname: Deal
authors.forename: Alan G
authors.initials: AG
authors.lastname: Zimmermann
authors.forename: Elena P
authors.initials: EP
authors.lastname: Shavrikova
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Child
authors.forename: Charmian A
authors.initials: CA
authors.lastname: Quigley
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Cutler
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001827:Body Height; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D011247:Pregnancy; D015995:Prevalence; D012307:Risk Factors; D013972:Thyrotropin / Q000097:blood
chemical_list: C583557:IGF1 protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin